Short RNA molecules, of about 21 to 24 nucleotides in length, have been shown to be involved in the mechanism of post transcriptional gene silencing in eukaryotes. These molecules are generated through the cleavage of long double stranded RNA molecules by RNAse III enzymes (DICER in animals; DICERLIKE in plants) and are used as guide-sequences incorporated in a RISC complex for the sequence-specific degradation of the target RNA (mRNA) molecules. The short RNA molecules can also be recruited in silencing complexes which interfere in a sequence specific manner with target gene expression by specific chromatin remodeling and methylation.
Recently, a novel class of short RNA molecules was discovered in animals and plants and named microRNA (miRNA). MicroRNAs are small endogenous RNAs that regulate gene expression in plants, but also in other eukaryotes. In plants, these about 21 nucleotide long RNAs are processed from the stem-loop regions of long endogenous primary transcripts by the cleavage activity of DCL1. Plant miRNAs are highly complementary to conserved target mRNAs, and guide the cleavage of their targets. miRNAs appear to be key components in regulating the gene expression of complex networks of pathways involved i.a. in development.
In animals, the biogenesis of miRNA from the longer primary transcripts (pri-miRNA) involves two steps. First, the miRNA stem-loop (pre-miRNA) is liberated from the pri-miRNA in the nucleus by cleavage on each arm of the stem-loop, effected by Drosha. After export to the cytoplasm, DICER makes a second set of cuts separating the miRNA (duplexed with its near reverse complement microRNA*) from the loop region of the pre-miRNA. In plants, both steps are carried out by DCL1 and presumably both steps occur in the nucleus.
International patent application WO 03/029459 described 22 and 21 nucleotide RNAs that function as key regulators in developmental timing in Caenorhabditis elegans. 
WO2004/009779 describes compositions and methods for modulating nucleotide sequence expression, particularly for modulating gene expression in plants. The compositions comprise precursor RNA constructs for the expression of an RNA precursor. The precursor RNA construct comprises a promoter that is expressed in a plant cell driving the expression of a precursor RNA having a microRNA. The miRNA is complementary or partially complementary to a portion of a target gene or nucleotide sequence and function to modulate expression of the target sequence or gene. In this manner, the RNA precursor construct can be designed to modulate expression of any nucleotide sequence of interest, either an endogenous plant gene or alternatively a transgene. The precursor RNA constructs may be used in combination with modulators to enhance the effect on gene expression. Expression of a modulator in the presence of the precursor RNA alters the accumulation of miRNAs and thus enhances the regulatory capabilities of miRNAs. The document further describes the use of a modulator to control gene expression via both siRNA and the miRNA pathway. Transformed plants, tissues, cells and seeds are also provided.
WO2005/017111 describes a method of identifying a microRNA-recognition element and of generating microRNAs as well as a system and computer programs for performing such methods. Recombinant nucleic acid molecule comprising a heterologous coding sequence and one or more MREs are also disclosed as are isolated nucleic acid molecule comprising one or more MRE sequences and being free of a coding sequence operably linked to regulatory elements. MicroRNA generated by a methods of the invention and the use of the microRNAs to downregulate gene expression are also described.
WO 2005/035769 and WO 2005/052170 provide methods and compositions useful in target sequence suppression and target sequence validation. The application also describes polynucleotide constructs useful for gene silencing, as well as cells, plants and seeds comprising the polynucleotides. Further provided is a method for using microRNA to silence a target sequence.
WO2005/047505 relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.
WO 2005/078096 is based, in part, on the discovery that endogenous miRNAs can be recruited for translational repression of target mRNAs. The RNA-silencing agents and the methods described herein, provide a means by which to treat genetic (e.g., genetic neurodegenerative diseases such as Huntington's Disease) or non-genetic diseases by, for example, blocking the synthesis of proteins that contribute to the diseases. Accordingly the described RNA-silencing agents have an mRNA targeting moiety, a linking moiety, and a miRNA recruiting moiety.
WO2005/100574 relates to means and methods for modifying biomass yield and/or plant growth and/or plant architecture of plants. In particular, it concerns transgenic plants exhibiting an increased biomass yield and plant growth rate compared to the corresponding wild-type plants. These plants are characterized by containing altered levels of a microRNA, in particular microRNA that targets members of the SPL family of genes encoding SPL transcription factors.
WO2006/034368 describes miRNAs, particularly from poplars, for plant growth and development.
WO2006/044322 describes methods and compositions useful in target sequence suppression, target sequence validation and target sequence down regulation. The document provides polynucleotide constructs useful for gene silencing or RNA down regulation, as well as cells, plants and seeds comprising the polynucleotides. Also provided is a method for using microRNA to silence a target sequence or to down regulate RNA.
Abreu et al. (2004, Genes and Development 18:2237-2242) describe in vivo investigation of the transcription, processing, endonucleolytic activity and functional relevance of the spatial distribution of a plant miRNA. To this end a synthetic miRNA miR171 targeting the coding region for GFP was constructed.
Schwab et al. (2005, Developmental Cell, 8: 517-527) describe specific effects of miRNAs on the plant transcriptome and deduced a set of empirical parameters for target recognition which could be applied to synthetic miRNAs.
Schwab et al. (2006, Plant Cell, 18(5):1121-1133) described highly specific gene silencing by artificial miRNAs, targeted to reduce the expression of different genes, in Arabidopsis. 
Alvarez et al 2006 (Plant Cell. 2006 May; 18(5):1134-1151) described that endogenous and synthetic microRNAs stimulate simultaneous, efficient and localized regulation of multiple targets in diverse species, including tobacco and tomato.
WO 00/04173 describes methods to modulate programmed cell death (PCD) in eukaryotic cells and organisms, particularly plant cells and plants, by introducing of “PCD modulating chimeric genes” influencing the expression and/or apparent activity of endogenous poly-(ADP-ribose) polymerase (PARP) genes. Programmed cell death may be inhibited or provoked. The invention particularly relates to the use of nucleotide sequences encoding proteins with PARP activity for modulating PCD, for enhancing growth rate or for producing stress tolerant cells and organisms.
WO 2004/090140 describes methods and means to increase the tolerance of plants to abiotic stress or adverse growing conditions, including drought, high light intensities, high temperatures, nutrient limitations and the like by reducing the activity of endogenous PARG proteins in plants.
WO2006/045633 describes the use of cotton parp2 gene or cDNA sequences to obtain stress tolerant cotton plants. Various cotton parp2 sequences are also provided.
None of the prior art documents describe miRNAs involved in the regulation of the response of plants to adverse abiotic conditions or the use thereof to modify the stress tolerance of plants. Neither do any of the prior art documents describe a synthetic miRNA which can be used to modify the stress tolerance of plants.
The aim of the current invention is to provide such stress-related miRNA molecules as well as synthetic miRNA molecules which can be used to modify or increase the tolerance of plants to adverse growing conditions and make them more resistant to stress conditions such as abiotic stress conditions.